Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of asthmatics.

Démoly, P.; Jaffuel, Dany; Lequeux, N; Weksler, BB; Créminon, Christophe; Michel, François; Godard, P.; Bousquet, Jean

doi:10.1164/ajrccm.155.2.9032211

Cited by 60 publications

(36 citation statements)

References 19 publications

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“…Demoly et al have recently reported PGHS-1 and PGHS-2 immunoreactivity in bronchial epithelium of normal and asthmatic humans (40). These results are distinctly different than recent in vitro data, which demonstrate that the dominant isoform in cultured human lung epithelial cells is PGHS-2 (41, 42).…”

Section: Discussionmentioning

confidence: 86%

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Gavett¹,

Madison²,

Chulada³

et al. 1999

J. Clin. Invest.

187

164

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To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1 -/-and PGHS-2 -/-mice. Among nonimmunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE 2 was dramatically reduced in bronchoalveolar lavage (BAL) fluid from PGHS-1 -/-mice, relative to wild-type or PGHS-2 -/-mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1 -/-mice compared with PGHS-2 -/-mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1 -/-and PGHS-2 -/-mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1 -/-mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE 2 in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE 2 in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2 -/-mice.

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Section: Discussionmentioning

confidence: 86%

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Gavett¹,

Madison²,

Chulada³

et al. 1999

J. Clin. Invest.

187

164

View full text Add to dashboard Cite

show abstract

“…In chronic inflammation, COX2 immunoreactivity was reported in the bronchial mucosa of normal and asthmatic lungs (20), as well as in the bronchial epithelium (21). The observed overexpression of COX2 in normal human lung fibroblasts is important, as it may drive inflammation and fibrotic conditions in lung (22).…”

Section: Discussionmentioning

confidence: 99%

PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation

Sun

Liu

Roth

et al. 2015

The Journal of Immunology

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Protein arginine methyltransferase (PRMT)1, methylating both histones and key cellular proteins, has emerged as a key regulator of various cellular processes. This study aimed to identify the mechanism that regulates PRMT1 in chronic Ag-induced pulmonary inflammation (AIPI) in the E3 rat asthma model. E3 rats were challenged with OVA for 1 or 8 wk to induce acute or chronic AIPI. Expression of mRNAs was detected by real-time quantitative PCR. PRMT1, TGF-β, COX2, and vascular endothelial growth factor protein expression in lung tissues was determined by immunohistochemistry staining and Western blotting. In the in vitro study, IL-4–stimulated lung epithelial cell (A549) medium (ISEM) with or without anti–TGF-β Ab was applied to human fibroblasts from lung (HFL1). The proliferation of HFL1 was determined by MTT. AMI-1 (pan-PRMT inhibitor) was administered intranasally to chronic AIPI rats to determine PRMT effects on asthmatic parameters. In lung tissue sections, PRMT1 expression was significantly upregulated, mainly in epithelial cells, in acute AIPI lungs, whereas it was significantly upregulated mainly in fibroblasts in chronic AIPI lungs. The in vitro study revealed that ISEM elevates PRMT1, COX2, and vascular endothelial growth factor expressions, and it promoted fibroblast proliferation. The application of anti–TGF-β Ab suppressed COX2 upregulation by ISEM. AMI-1 inhibited the expression of COX2 in TGF-β–stimulated cells. In the in vivo experiment, AMI-1 administered to AIPI rats reduced COX2 production and humoral immune response, and it abrogated mucus secretion and collagen generation. These findings suggested that TGF-β–induced PRMT1 expression participates in fibroblast proliferation and chronic airway inflammation in AIPI.

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“…The enzyme COX-2 is induced during inflammation and is involved in the synthesis of prostaglandins, converting arachidonic acid to prostaglandin H 2 [38]. Its expression, which is localised to the bronchial epithelium and submucosal inflammatory cells, is reported to be increased in expression in mild asthma and aspirin-sensitive asthma compared with healthy controls [39][40][41]. To the best of our knowledge, there are no reports of its expression levels in severe asthma.…”

Section: Discussionmentioning

confidence: 99%

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study

et al. 2016

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on behalf of the U-BIOPRED Study Group 16ABSTRACT The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild-moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm , p<0.001) groups. No other differences were observed. Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall. @ERSpublications Severe asthma exists despite suppressed tissue inflammation in proximal airways when on current recommended therapy

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Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of asthmatics.

Cited by 60 publications

References 19 publications

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

Allergic lung responses are increased in prostaglandin H synthase–deficient mice

PRMT1 Upregulated by Epithelial Proinflammatory Cytokines Participates in COX2 Expression in Fibroblasts and Chronic Antigen-Induced Pulmonary Inflammation

Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study

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